Serotonin [5-hydroxytryptamine (hereinafter occasionally abbreviated as “5-HT”)] is a neurotransmitter in living bodies, and it has been known that there exist seven kinds of subtypes thereof (5-HT1 to 5-HT7). Among them, 5-HT3 receptor has been elucidated to be involved in nausea and vomition as the side effects of carcinostatic agents such as cisplatin and radiotherapy, and 5-HT3 receptor antagonists have been clinically used as antiemetic agents. Specifically, examples include Granisetron [Sanger, G. J. et al., Eur. J. Pharmacol., 159, 113–124 (1989)], Ondansetron (GR38032F) [Butler, A. et al., Br. J. Pharmacol., 94, 387–412 (1988)], and Tropisetron [Richardson, B. P. et al., Nature, 316, 136–131 (1985)]. It has recently been reported that compounds having 5-HT3 receptor antagonistic activity are effective for preventive and/or therapeutic treatment of irritable bowel syndrome and the like [Greenshaw, A. J. et al., Drugs, 53, 20–39 (1997), and Greenshaw, A. J. et al., Trends Pharmacol. Sci., 14, 265–270 (1993)], and development of Alosetron is presently attempted (Japanese Patent Publication (KOKAI) No. 1-151578/1989).
However, when a compound having only the 5-HT3 receptor antagonistic activity is administered to the digestive tract as a preventive and/or therapeutic medicament for irritable bowel syndrome or digestive tract functional disorder, the administration may likely cause a problem of constipation as a side effect, although diarrhea is inhibited. As one of the means for solving this problem, the inventors of the present invention provided benzoxazole derivatives which have 5-HT3 receptor activating action in addition to the 5-HT3 receptor antagonistic activity (Japanese Patent Publication (KOKAI) No. 10-29987/1998). As compounds which similarly have both of the 5-HT3 receptor antagonistic activity and the 5-HT3 receptor activating action, MKC-733 (Japanese Patent Publication (KOKAI) No. 5-310747/1993) and RS-056812-198 [J. A. VanHooft et al., Eur. J. Pharmacol., 322, 229–233 (1997)], are also disclosed.
No compound is reported which exhibits potent inhibitory action against diarrhea without causing the side effect of constipation and is not easily metabolized in living bodies, when it is used as preventive and/or therapeutic medicaments for irritable bowel syndrome or digestive tract functional disorder. Therefore, it has been desired to develop compounds having such characteristic features.